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1.
Chem Biodivers ; : e202401179, 2024 May 29.
Artículo en Inglés | MEDLINE | ID: mdl-38808458

RESUMEN

Natural polybrominated diphenyl ethers are generally isolated from sponges and possess a broad range of biological activities. Through screening of our marine natural product library, we discovered that polybrominated diphenyl ethers 5 and 6 exhibit considerable anti-inflammatory activity. In order to expand our repertoire of derivatives for further biological activity studies, we designed and synthesized a series of 5-related polybrominated diphenyl ethers. Importantly, compound 5a showed comparable anti-inflammatory activity while much lower cytotoxicity on lipopolysaccharide (LPS)-induced RAW264.7 cells. Additionally, western blotting analysis showed that 5a reduced the expression of phosphorylated extracellular signal-regulated kinase (p-ERK). Besides, molecular docking experiments were conducted to predict and elucidate the potential mechanisms underlying the varying anti-inflammatory activities exhibited by compounds 5a, 5, and 6.

2.
Int J Mol Sci ; 25(5)2024 Feb 21.
Artículo en Inglés | MEDLINE | ID: mdl-38473774

RESUMEN

The mutualistic symbiosis relationship between the gut microbiome and their insect hosts has attracted much scientific attention. The native woodwasp, Sirex nitobei, and the invasive European woodwasp, Sirex noctilio, are two pests that infest pines in northeastern China. Following its encounter with the native species, however, there is a lack of research on whether the gut microbiome of S. noctilio changed, what causes contributed to these alterations, and whether these changes were more conducive to invasive colonization. We used high-throughput and metatranscriptomic sequencing to investigate S. noctilio larval gut and frass from four sites where only S. noctilio and both two Sirex species and investigated the effects of environmental factors, biological interactions, and ecological processes on S. noctilio gut microbial community assembly. Amplicon sequencing of two Sirex species revealed differential patterns of bacterial and fungal composition and functional prediction. S. noctilio larval gut bacterial and fungal diversity was essentially higher in coexistence sites than in separate existence sites, and most of the larval gut bacterial and fungal community functional predictions were significantly different as well. Moreover, temperature and precipitation positively correlate with most of the highly abundant bacterial and fungal genera. Source-tracking analysis showed that S. noctilio larvae at coexistence sites remain dependent on adult gut transmission (vertical transmission) or recruitment to frass (horizontal transmission). Meanwhile, stochastic processes of drift and dispersal limitation also have important impacts on the assembly of S. noctilio larval gut microbiome, especially at coexistence sites. In summary, our results reveal the potential role of changes in S. noctilio larval gut microbiome in the successful colonization and better adaptation of the environment.


Asunto(s)
Microbioma Gastrointestinal , Microbiota , Pinus , Avispas , Animales , Avispas/microbiología , Larva
3.
Chem Biodivers ; 20(6): e202300616, 2023 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-37232046

RESUMEN

Two new glycerolipids, syngaculipids A and B (1 and 2), one first naturally occurring metabolite (8), together with five known compounds (3-7) were isolated from the AcOEt fraction of Syngnathus acus L. (Hai-Long). Their structures were elucidated by comprehensive spectral analyses involving UV, IR, MS, 1D and 2D NMR spectra and ECD calculations. All the isolated compounds were evaluated for their cytotoxicity against A549 and HCT-116 cell lines. Compound 8 exhibited moderate cytotoxicity with IC50 values of 34.5 and 38.9 µM on the A549 and HCT-116 cell lines, respectively.


Asunto(s)
Medicina Tradicional China , Humanos , Estructura Molecular , Células HCT116
4.
Pharmacol Res ; 169: 105640, 2021 07.
Artículo en Inglés | MEDLINE | ID: mdl-33915296

RESUMEN

AIM: Brain microvascular endothelial cells (BMVECs), as the important structure of blood-brain barrier (BBB), play a vital role in ischemic stroke. Pyroptosis of different cells in the brain may aggravate cerebral ischemic injury, and PGC-1α plays a major role in pyroptosis. However, it is not known whether BMVECs undergo pyroptosis after ischemic stroke and whether PGC-1α activator Medioresinol (MDN) we discovered may be useful against pyroptosis of endothelial cells and ischemic brain injury. METHODS: For in vitro experiments, the bEnd.3 cells and BMVECs under oxygen and glucose-deprivation (OGD) were treated with or without MDN, and the LDH release, tight junction protein degradation, GSDMD-NT membrane location and pyroptosis-associated proteins were evaluated. For in vivo experiments, mice underwent transient middle cerebral artery occlusion (tMCAO) for ischemia model, and the neuroprotective effects of MDN were measured by infarct volume, the permeability of BBB and pyroptosis of BMVECs. For mechanistic study, effects of MDN on the accumulation of phenylalanine, mitochondrial reactive oxygen species (mtROS) were tested by untargeted metabolomics and MitoSOX Red probe, respectively. RESULTS: BMVECs underwent pyroptosis after ischemia. MDN dose-dependently activated PGC-1α, significantly reduced pyroptosis, mtROS and the expressions of pyroptosis-associated proteins (NLRP3, ASC, cleaved caspase-1, IL-1ß, GSDMD-NT), and increased ZO-1 and Occludin protein expressions in BMVECs. In tMCAO mice, MDN remarkably reduced brain infarct volume and the permeability of BBB, inhibited pyroptosis of BMVECs, and promoted long-term neurobehavioral functional recovery. Mechanistically, MDN promoted the interaction of PGC-1α with PPARα to increase PPARα nuclear translocation and transcription activity, further increased the expression of GOT1 and PAH, resulting in enhanced phenylalanine metabolism to reduce the ischemia-caused phenylalanine accumulation and mtROS and further ameliorate pyroptosis of BMVECs. CONCLUSION: In this study, we for the first time discovered that pyroptosis of BMVECs was involved in the pathogenesis of ischemic stroke and MDN as a novel PGC-1α activator could ameliorate the pyroptosis of endothelial cells and ischemic brain injury, which might attribute to reduction of mtROS through PPARα/GOT1 axis in BMVECs. Taken together, targeting endothelial pyroptosis by MDN may provide alternative therapeutics for brain ischemic stroke.


Asunto(s)
Aspartato Aminotransferasa Citoplasmática/metabolismo , Endotelio Vascular/efectos de los fármacos , Accidente Cerebrovascular Isquémico/tratamiento farmacológico , Lignanos/uso terapéutico , Fármacos Neuroprotectores/uso terapéutico , PPAR alfa/metabolismo , Coactivador 1-alfa del Receptor Activado por Proliferadores de Peroxisomas gamma/agonistas , Piroptosis/efectos de los fármacos , Animales , Inmunoprecipitación de Cromatina , Modelos Animales de Enfermedad , Endotelio Vascular/metabolismo , Técnica del Anticuerpo Fluorescente , Cromatografía de Gases y Espectrometría de Masas , Células HEK293/efectos de los fármacos , Humanos , Lignanos/farmacología , Masculino , Potencial de la Membrana Mitocondrial/efectos de los fármacos , Ratones , Ratones Endogámicos ICR , Fármacos Neuroprotectores/farmacología , Ratas Sprague-Dawley
5.
Angew Chem Int Ed Engl ; 59(6): 2429-2439, 2020 02 03.
Artículo en Inglés | MEDLINE | ID: mdl-31782597

RESUMEN

Benzoxepane derivatives were designed and synthesized, and one hit compound emerged as being effective in vitro with low toxicity. In vivo, this hit compound ameliorated both sickness behavior through anti-inflammation in LPS-induced neuroinflammatory mice model and cerebral ischemic injury through anti-neuroinflammation in rats subjected to transient middle cerebral artery occlusion. Target fishing for the hit compound using photoaffinity probes led to identification of PKM2 as the target protein responsible for anti-inflammatory effect of the hit compound. Furthermore, the hit exhibited an anti-neuroinflammatory effect in vitro and in vivo by inhibiting PKM2-mediated glycolysis and NLRP3 activation, indicating PKM2 as a novel target for neuroinflammation and its related brain disorders. This hit compound has a better safety profile compared to shikonin, a reported PKM2 inhibitor, identifying it as a lead compound in targeting PKM2 for the treatment of inflammation-related diseases.


Asunto(s)
Antiinflamatorios/síntesis química , Dibenzoxepinas/química , Animales , Antiinflamatorios/farmacología , Antiinflamatorios/uso terapéutico , Dibenzoxepinas/farmacología , Dibenzoxepinas/uso terapéutico , Modelos Animales de Enfermedad , Infarto de la Arteria Cerebral Media/complicaciones , Infarto de la Arteria Cerebral Media/patología , Interleucina-1beta/genética , Interleucina-1beta/metabolismo , Accidente Cerebrovascular Isquémico/tratamiento farmacológico , Accidente Cerebrovascular Isquémico/etiología , Lipopolisacáridos/toxicidad , Macrófagos/citología , Macrófagos/efectos de los fármacos , Macrófagos/metabolismo , Ratones , Microglía/citología , Microglía/efectos de los fármacos , Microglía/metabolismo , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Naftoquinonas/uso terapéutico , Piruvato Quinasa/antagonistas & inhibidores , Piruvato Quinasa/metabolismo , Células RAW 264.7 , Ratas , Relación Estructura-Actividad , Factor de Necrosis Tumoral alfa/genética , Factor de Necrosis Tumoral alfa/metabolismo
6.
Sheng Wu Yi Xue Gong Cheng Xue Za Zhi ; 36(4): 627-632, 2019 Aug 25.
Artículo en Zh | MEDLINE | ID: mdl-31441264

RESUMEN

The quality inspection of magnetic resonance imaging (MRI) performance parameters is an important means to ensure the image quality and the reliability of diagnosis results. There are some problems in the manual calculation and eye recognition of the quality inspection parameters, such as strong subjectivity and low efficiency. In view of these facts, an automatic analysis system for MRI quality detection based on QT is proposed and implemented in C++ language. The image processing algorithm is introduced to automatically measure and calculate the quality inspection parameters. The software with comprehensive functions is designed to systematically manage the quality inspection information of MRI. The experimental results show that the automatically calculated parameters are consistent with the manually calculated ones. Accordingly, the accuracy and reliability of the algorithm is verified. The whole system is efficient, convenient and easy to operate, and it can meet the actual needs of MRI quality inspection.


Asunto(s)
Procesamiento de Imagen Asistido por Computador , Imagen por Resonancia Magnética/normas , Algoritmos , Reproducibilidad de los Resultados
7.
BMC Genomics ; 17: 651, 2016 Aug 18.
Artículo en Inglés | MEDLINE | ID: mdl-27538507

RESUMEN

BACKGROUND: Eogystia hippophaecolus (Hua et al.) (Lepidoptera: Cossidae) is the major threat to seabuckthorn plantations in China. Specific and highly efficient artificial sex pheromone traps was developed and used to control it. However, the molecular basis for the pheromone recognition is not known. So we established the antennal transcriptome of E. hippophaecolus and characterized the expression profiles of odorant binding proteins. These results establish and improve the basis knowledge of the olfactory receptive system, furthermore provide a theoretical basis for the development of new pest control method. RESULTS: We identified 29 transcripts encoding putative odorant-binding proteins (OBPs), 18 putative chemosensory proteins (CSPs), 63 odorant receptors (ORs), 13 gustatory receptors (GRs), 12 ionotropic receptors (IRs), and two sensory neuron membrane proteins (SNMPs). Based on phylogenetic analysis, we found one Orco and three pheromone receptors of E. hippophaecolus and found that EhipGR13 detects sugar, EhipGR11 and EhipGR3 detect bitter. Nine OBPs expression profile indicated that most were the highest expression in antennae, consistent with functions of OBPs in binding and transporting odors during the antennal recognition process. OBP6 was external expressed in male genital-biased in, and this locus may be responsible for pheromone binding and recognition as well as mating. OBP1 was the highest and biased expressed in the foot and may function as identification of host plant volatiles. CONCLUSIONS: One hundred thirty-seven chemosensory proteins were identified and the accurate functions and groups of part proteins were obtained by phylogenetic analysis. The most OBPs were antenna-biased expressed, which are involved in antennal recognition. However, few OBP was detected biased expression in the foot and external genitalia, and these loci may function in pheromone recognition, mating, and the recognition of plant volatiles.


Asunto(s)
Antenas de Artrópodos/metabolismo , Perfilación de la Expresión Génica/métodos , Lepidópteros/genética , Receptores Odorantes/genética , Animales , Regulación de la Expresión Génica , Ontología de Genes , Proteínas de Insectos/genética , Proteínas de Insectos/metabolismo , Masculino , Filogenia , Receptores Odorantes/metabolismo , Receptores de Feromonas/genética , Receptores de Feromonas/metabolismo , Análisis de Secuencia de ADN
8.
Insects ; 15(7)2024 Jun 27.
Artículo en Inglés | MEDLINE | ID: mdl-39057211

RESUMEN

Sirex noctilio, a European woodwasp, occasionally shares resources with the native S. nitobei and other colonizers in northeast China. The impact of its coexistence on individual species remains unclear. Random sampling was conducted to assess the patterns and extent of insect co-colonization across various spatial scales. Additionally, we analyzed wood sections to determine the density, adult size, and distribution of the two Sirex species. Spatial scales revealed negative associations (Asemum striatum and Phaenops sp.) and neutral ones (Ips acuminatus) between woodwasps and other co-colonizers. Clustering of woodwasps and Phaenops sp. occurred at a small scale (0-7.3 m). Regression analysis showed a positive correlation between the chance of woodwasp attacks and past attacks on the same host, with little impact from other colonization factors. The distribution and body size of S. noctilio within the tree appeared unaffected by S. nitobei's presence. In the presence of S. noctilio, S. nitobei tended to lay eggs in damaged sections. At the stand level, the overall impact of S. noctilio on S. nitobei population density is likely positive because S. nitobei prefer weaker trees, a preference potentially influenced by initial attacks from S. noctilio on healthier hosts.

9.
Front Microbiol ; 15: 1341646, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39056012

RESUMEN

In northeast China, the invasive woodwasp., Sirex noctilio, attacks Pinus sylvestris var. mongolica Litv and often shares habitat with native Sirex nitobei. Previous research showed that S. noctilio can utilize the volatiles from its symbiotic fungus (A. areolatum IGS-BD) to locate host trees. Consequently, symbiotic fungi (A. areolatum IGS-D and A. chailletii) carried by S. nitobei may influence the behavioral selection of S. noctilio. This study aimed to investigate the impact of fungal odor sources on S. noctilio's behavior in laboratory and field experiments. Our observations revealed that female woodwasps exhibited greater attraction toward the fungal volatiles of 14-day-old Amylostereum IGS-D in a "Y"-tube olfactometer and wind tunnel. When woodwasps were released into bolts inoculated separately with three strains in the field, females of S. noctilio exhibited a preference for those bolts pre-inoculated with A. areolatum IGS-BD. Gas chromatography-mass spectrometry (GC-MS) analysis revealed that the volatiles emitted by the two genotypes of A. areolatum were similar yet significantly distinct from those of Ampelopsis chailletii. Hence, we postulate that the existence of native A. areolatum IGS-D could potentially facilitate the colonization of S. noctilio in scenarios with minimal or no A. areolatum IGS-BD present in the host.

10.
Adv Sci (Weinh) ; : e2404558, 2024 Jul 04.
Artículo en Inglés | MEDLINE | ID: mdl-38965690

RESUMEN

Harmonic generation and utilization are significant topics in nonlinear science. Although the progress in the microwave region has been expedited by the development of time-modulated metasurfaces, one major issue of these devices is the strong entanglement of multiple harmonics, leading to criticism of their use in frequency-division multiplexing (FDM) applications. Previous studies have attempted to overcome this limitation, but they suffer from designing complexity or insufficient controlling capability. Here a new space-time-coding metasurface (STCM) is proposed to independently and precisely synthesize not only the phases but also the amplitudes of various harmonics. This promising feature is successfully demonstrated in wireless space- and frequency-division multiplexing experiments, where modulated and unmodulated signals are simultaneously transmitted via different harmonics using a shared STCM. To illustrate the advantages, binary frequency shift keying (BFSK) and quadrature phase shift keying (QPSK) modulation schemes are respectively implemented. Behind the intriguing functionality, the mechanism of the space-time coding strategy and the analytical designing method are elaborated, which are validated numerically and experimentally. It is believed that the achievements can potentially propel the time-vary metasurfaces in the next-generation wireless applications.

11.
J Med Chem ; 67(14): 12248-12260, 2024 Jul 25.
Artículo en Inglés | MEDLINE | ID: mdl-38959374

RESUMEN

Cembranolides are characteristic metabolites in marine soft corals, with complex structures and widespread biological activities. However, seldom has an intensive pharmacological study been done for these intriguing marine natural products. In this work, systematic chemical investigation was performed on Sinularia pedunculata by HSQC-based small molecule accurate recognition technology (SMART), resulting in the isolation and identification of 31 cembrane-type diterpenoids, including six new ones. In the bioassay, several compounds showed significant anti-inflammatory activities on the inhibition of NO production. The structure-activity relationship (SAR) was comprehensively analyzed, and two most bioactive and less toxic compounds 8 and 9 could inhibit inflammation through suppressing NF-κB and MAPK signaling pathways, and reduce the secretion of inflammatory cytokines. In a mouse model of dextran sodium sulfate (DSS)-induced acute colitis, 8 and 9 exhibited good anti-inflammatory effects and the ability to repair the colon epithelium, giving insight into the application of cembranolides as potential ulcerative colitis (UC) agents.


Asunto(s)
Antozoos , Colitis Ulcerosa , Sulfato de Dextran , Diterpenos , Animales , Colitis Ulcerosa/tratamiento farmacológico , Diterpenos/farmacología , Diterpenos/química , Diterpenos/uso terapéutico , Diterpenos/aislamiento & purificación , Ratones , Relación Estructura-Actividad , Antozoos/química , Antiinflamatorios/farmacología , Antiinflamatorios/química , Antiinflamatorios/uso terapéutico , Antiinflamatorios/aislamiento & purificación , Células RAW 264.7 , FN-kappa B/metabolismo , FN-kappa B/antagonistas & inhibidores , Descubrimiento de Drogas , Ratones Endogámicos C57BL , Humanos , Masculino , Óxido Nítrico/metabolismo
12.
Insects ; 13(4)2022 Mar 30.
Artículo en Inglés | MEDLINE | ID: mdl-35447780

RESUMEN

Sirex noctilio is a major international quarantine pest that recently emerged in northeast China to specifically invade conifers. During female oviposition, venom is injected into the host together with its symbiotic fungus to alter the normal Pinus physiology and weaken or even kill the tree. In China, the Mongolian pine (Pinus sylvestris var. mongolica), an important wind-proof and sand-fixing species, is the unique host of S. noctilio. To explore the interplay between S. noctilio venom and Mongolian pine, we performed a transcriptome comparative analysis of a 10-year-old Mongolian pine after wounding and inoculation with S. noctilio venom. The analysis was performed at 12 h, 24 h and 72 h. PacBio ISO-seq was used and integrated with RNA-seq to construct an accurate full-length transcriptomic database. We obtained 52,963 high-precision unigenes, consisting of 48,654 (91.86%) unigenes that were BLASTed to known sequences in the public database and 4309 unigenes without any annotation information, which were presumed to be new genes. The number of differentially expressed genes (DEGs) increased with the treatment time, and the DEGs were most abundant at 72 h. A total of 706 inoculation-specific DEGs (475 upregulated and 231 downregulated) and 387 wounding-specific DEGs (183 upregulated and 204 downregulated) were identified compared with the control. Under venom stress, we identified 6 DEGs associated with reactive oxygen species (ROS) and 20 resistance genes in Mongolian pine. Overall, 52 transcription factors (TFs) were found under venom stress, 45 of which belonged to the AP2/ERF TF family and were upregulated. A total of 13 genes related to the photosystem, 3 genes related photo-regulation, and 9 TFs were identified under wounding stress. In conclusion, several novel putative genes were found in Mongolian pine by PacBio ISO seq. Meanwhile, we also identified various genes that were resistant to S. noctilio venom, such as GAPDH, GPX, CAT, FL2, CERK1, and HSP83A, etc.

13.
Chin J Nat Med ; 20(1): 74-80, 2022 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-35101252

RESUMEN

Diversity-oriented synthesis is aimed to increase the chemical diversity of target natural products for extensive biological activity evaluation. Indole ring is an important functional group in a large number of drugs and other biologically active agents, and indole-containing natural products have been frequently isolated from marine sources in recent years. In this paper, a series of indole-containing marine natural hyrtioreticulin derivatives, including 19 new ones, were designed, synthesized through a key Pictet-Spengler reaction, and evaluated for their inflammation related activity. Compound 13b displayed the most promising activity by inhibiting TNF-α cytokine release with an inhibitory rate of 92% at a concentration of 20 µmol·L-1. A preliminary structure-activity relationship analysis was also discussed. This research may throw light on the discovery of marine indole alkaloid derived anti-inflammatory drug leads.


Asunto(s)
Productos Biológicos , Poríferos , Animales , Antiinflamatorios/farmacología , Productos Biológicos/farmacología , Alcaloides Indólicos/farmacología , Relación Estructura-Actividad
14.
J Fungi (Basel) ; 7(12)2021 Dec 11.
Artículo en Inglés | MEDLINE | ID: mdl-34947047

RESUMEN

Sirex noctilio along with its mutualistic fungal symbiont, Amylostereum areolatum (a white rot fungus), is an invasive pest that causes excessive damage to Pinus plantations in Northeast China. In 2015, S. noctilio were found to attack Pinus sylvestris var. mongolica, and often share larval habitat with the native woodwasp, S. nitobei. The objective of this study was to determine the possible origin(s) of the introduced pest complex in China and analyse the genetic diversity between A. areolatum isolated from invasive S. noctilio, native S. nitobei and other woodwasps collected from Europe (native range) and other countries. Phylogenetic analyses were performed using the intergenic spacer (IGS) dataset and the combined 4-locus dataset (the internal transcribed spacer region (ITS), translation elongation factor alpha 1 (tef1), DNA-directed ribosomal polymerase II (RPB2), and mitochondrial small subunit (mtSSU)) of three Amylostereum taxa. The multilocus genotyping of nuclear ribosomal regions and protein coding genes revealed at least three distinct multilocus genotypes (MLGs) of the fungus associated with invasive S. noctilio populations in Northeast China, which may have come from North America or Europe. The IGS region of A. areolatum carried by S. noctilio from China was designated type B1D2. Our results showed a lack of fidelity (the paradigm of obligate fidelity to a single fungus per wasp species) between woodwasp hosts and A. areolatum. We found that the native S. nitobei predominantly carried A. areolatum IGS-D2, but a low percentage of females instead carried A. areolatum IGS-B1D2 (MLG A13), which was presumably due to horizontal transmission from S. noctilio, during the sequential use of the same wood for larval development. The precise identification of the A. areolatum genotypes provides valuable insight into co-evolution between Siricidae and their symbionts, as well as understanding of the geographical origin and history of both Sirex species and their associated fungi.

15.
Acta Pharm Sin B ; 11(3): 708-726, 2021 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-33777677

RESUMEN

Ischemic stroke is the second leading cause of death worldwide with limited medications and neuroinflammation was recognized as a critical player in the progression of stroke, but how to control the overactive neuroinflammation is still a long-standing challenge. Here, we designed a novel SIRT6 activator MDL-811 which remarkably inhibited inflammatory response in lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages and primary mouse microglia, which were abolished by silencing SIRT6. RNA-seq screening identified the forkhead box C1 (Foxc1) is a key gene evoked by MDL-811 stimulation and is required for the anti-inflammatory effects of MDL-811. We found MDL-811-activated SIRT6 directly interacted with enhancer of zeste homolog 2 (EZH2) and promoted deacetylation of EZH2 which could bind to the promoter of Foxc1 and upregulate its expression to modulate inflammation. Moreover, our data demonstrated that MDL-811 not only ameliorated sickness behaviors in neuroinflammatory mice induced by LPS, but also markedly reduced the brain injury in ischemic stroke mice in addition to promoting long-term functional recovery. Importantly, MDL-811 also exhibited strong anti-inflammatory effects in human monocytes isolated from ischemic stroke patients, underlying an interesting translational perspective. Taken together, MDL-811 could be an alternative therapeutic candidate for ischemic stroke and other brain disorders associated with neuroinflammation.

16.
Acta Pharm Sin B ; 11(7): 1867-1884, 2021 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-34386325

RESUMEN

Blood-brain barrier (BBB) damage after ischemia significantly influences stroke outcome. Compound LFHP-1c was previously discovered with neuroprotective role in stroke model, but its mechanism of action on protection of BBB disruption after stroke remains unknown. Here, we show that LFHP-1c, as a direct PGAM5 inhibitor, prevented BBB disruption after transient middle cerebral artery occlusion (tMCAO) in rats. Mechanistically, LFHP-1c binding with endothelial PGAM5 not only inhibited the PGAM5 phosphatase activity, but also reduced the interaction of PGAM5 with NRF2, which facilitated nuclear translocation of NRF2 to prevent BBB disruption from ischemia. Furthermore, LFHP-1c administration by targeting PGAM5 shows a trend toward reduced infarct volume, brain edema and neurological deficits in nonhuman primate Macaca fascicularis model with tMCAO. Thus, our study identifies compound LFHP-1c as a firstly direct PGAM5 inhibitor showing amelioration of ischemia-induced BBB disruption in vitro and in vivo, and provides a potentially therapeutics for brain ischemic stroke.

17.
Front Microbiol ; 12: 641141, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33897646

RESUMEN

The European woodwasp, Sirex noctilio Fabricius, is a major invasive quarantine pest that attacks and kills pine trees outside of its native range. Insect gut structure and gut microbiota play crucial roles in various life activities. Despite a few reports in nutrition and survival, an extensive study on the S. noctilio larval gut microbiome is lacking. We studied the gut structure using a stereo microscope and used high throughput sequencing of the bacterial 16S rRNA genes and fungal internal transcribed spacer 2 (ITS2) regions to investigate gut microbiota in different developmental stages of S. noctilio, including larvae, adults, and larval frass. We used PICRUSt2 to predict the functional profiles. The larval gut was thin and thread-like from the oral cavity to the anus, carrying few xylem particles in the crop. Pseudomonas, Ralstonia, and Burkholderia s.l were the dominant bacteria in the guts of larvae, adults, and frass, respectively. Even though Pseudomonas was the most abundant among all bacteria, Zoogloea, Ruminobacter, and Nitrosospira, which might be involved in degrading organic matter and fixing nitrogen occurred exclusively in the larval gut indicating their possible role in the growth and development of larvae in pine tree xylem. Fungal communities did not change significantly across different developmental stages or the frass. Amylostereum was dominant in the woodwasp's larval gut. Functional prediction of bacterial and fungal communities revealed that they may encod enzymes involved in degrading lignocellulose and fixing nitrogen. Ours is the first study that compares gut microbial communities present in S. noctilio larvae, adults, and frass. This study could provide an understanding of larval nutrient acquisition in nutrient-deficient host xylem to some extent. Our study may unlock novel strategies for the development of pest management approaches based on interfering with the gut microbiota and restricting their role in larval survival and development.

18.
Toxins (Basel) ; 13(8)2021 08 11.
Artículo en Inglés | MEDLINE | ID: mdl-34437434

RESUMEN

The wood-boring woodwasp Sirex nitobei is a native pest in Asia, infecting and weakening the host trees in numerous ecological and commercial coniferous forest plantations. In China, hosts of S. nitobei are diverse, so the pest has spread to several provinces of China, resulting in considerable economic and ecological damage. During female oviposition, S. nitobei venom along with arthrospores of the symbiotic fungus Amylostereum areolatum or A. chaetica is injected into host trees, and the combination of these two biological factors causes the death of xylem host trees. The presence of venom alone causes only the yellowing and wilting of needles. In this study, we constructed the venom gland transcriptome of S. nitobei for the first time and a total of 15,036 unigenes were acquired. From the unigenes, 11,560 ORFs were identified and 537 encoding protein sequences with signal peptides at the N-terminus. Then, we used the venomics approach to characterize the venom composition of female S. nitobei and predicted 1095 proteins by liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis. We focused on seven proteins that were both highly expressed in the venom gland transcriptome and predicted in the crude venom proteome. These seven proteins are laccase-2, laccase-3, a protein belonging to the Kazal family, chitooligosaccharidolytic ß-N-acetylglucosaminidase, beta-galactosidase, icarapin-like protein, and waprin-Thr1-like protein. Using quantitative real-time PCR (qRT-PCR), we also proved that the genes related to these seven proteins are specifically expressed in the venom glands. Finally, we revealed the functional role of S. nitobei venom in the physiological response of host trees. It can not only promote the colonization of symbiotic fungus but contribute to the development of eggs and larvae. This study provides a deeper understanding of the molecular mechanism of the woodwasp-pine interaction.


Asunto(s)
Glándulas Exocrinas/metabolismo , Proteínas de Insectos , Venenos de Avispas , Avispas , Animales , Basidiomycota , Femenino , Perfilación de la Expresión Génica , Interacciones Huésped-Parásitos , Proteínas de Insectos/genética , Proteínas de Insectos/metabolismo , Masculino , Pinus/microbiología , Enfermedades de las Plantas , Proteoma/análisis , Proteoma/genética , Transcriptoma , Venenos de Avispas/química , Venenos de Avispas/genética , Avispas/genética , Avispas/metabolismo
19.
Artículo en Inglés | MEDLINE | ID: mdl-32544860

RESUMEN

The moth Eogystia hippophaecolus (Hua et al.) is a major threat to sea buckthorn plantations in China. Specific and highly efficient artificial sex pheromone traps have been developed and used to control this pest species. However, the biosynthesis of sex pheromones Z7-14: Ac and E3-14:Ac remains poorly understood. We investigated the female pheromone gland transcriptome of E. hippophaecolus and identified two pheromone biosynthesis-activating neuropeptides (PBANs), two pheromone biosynthesis-activating neuropeptide receptors (PBANrs), five acetyl-CoA carboxylases (ACCs), six fatty acid synthases (FASs), 16 Acyl-CoA desaturases (DESs), 26 reductases (REDs), 13 acetyltransferases (ACTs), one fatty acid transport protein (FATP), one acyl-CoA-binding protein (ACBP), and five elongation of very long-chain fatty acid proteins (ELOs) in pheromone biosynthesis pathways. Additionally, we identified 11 odorant-degrading enzymes (ODEs) and 16 odorant-binding proteins (OBPs), 14 chemosensory proteins (CSPs), two sensory neuron membrane proteins (SNMPs), three odorant receptors (ORs), seven ionotropic receptors (IRs), and six gustatory receptors (GRs). 77 unigenes involved in female pheromone biosynthesis, 31 chemoreception proteins and 11 odorant degradation enzymes were identified, which provided insight into the regulation of the pheromone components and pheromone recognition in the sex pheromone gland, and knowledge pertinent to new integrated pest management strategy of interference pheromone biosynthesis and recognition.


Asunto(s)
Vías Biosintéticas , Proteínas de Insectos/metabolismo , Mariposas Nocturnas/metabolismo , Feromonas/metabolismo , Atractivos Sexuales/metabolismo , Animales , Femenino , Proteínas de Insectos/genética , Mariposas Nocturnas/genética , Feromonas/genética , Atractivos Sexuales/genética , Transcriptoma
20.
Insects ; 11(2)2020 Jan 24.
Artículo en Inglés | MEDLINE | ID: mdl-31991571

RESUMEN

Sirex noctilio F. (Hymenoptera: Siricidae) is an invasive woodwasp from Europe and North Africa. Globalization has led to an expanding global presence in pine forests. S. noctilio has been previously introduced outside of its native range and now co-occurs in trees with native S. nitobei Matsumura (first discovered in 2016). Damage to Pinus sylvestris var. mongolica Litv in northeast China can be attributed to two types of woodwasp. To distinguish the two species by the traditional taxonomic morphology, we mainly differentiate the color of the male's abdomen and the female's leg. There remains intraspecific variation like leg color in the delimitation of related genera or sibling species of Sirex woodwasps. In this study, we used landmark-based geometric morphometrics including principal component analysis, canonical variate analysis, thin-plate splines, and cluster analysis to analyze and compare the wings, ovipositors, and cornus of two woodwasps to ascertain whether this approach is reliable for taxonomic studies of this group. The results showed significant differences in forewing venation and the shapes of pits in the middle of ovipositors among the two species, whereas little difference in hindwings and cornus was observed. This study assists in clarifying the taxonomic uncertainties of Siricidae and lays a foundation for further studies of the interspecific relationships of the genus Sirex.

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